Haiyang Tang, Akash Gupta, Seth A Morrisroe, Changlei Bao, Tae-Hwi Schwantes-An, Geetanjali Gupta, Shuxin Liang, Yanan Sun, Aiai Chu, Ang Luo, Venkateswaran Ramamoorthi Elangovan, Shreya Sangam, Yinan Shi, Samisubbu R Naidu, Jia-Rong Jheng, Sultan Ciftci-Yilmaz, Noel A Warfel, Louise Hecker, Sumegha Mitra, Anna W Coleman, Katie A Lutz, Michael W Pauciulo, Yen-Chun Lai, Ali Javaheri, Rohan Dharmakumar, Wen-Hui Wu, Daniel P Flaherty, Jason H Karnes, Sandra Breuils-Bonnet, Olivier Boucherat, Sebastien Bonnet, Jason X-J Yuan, Jeffrey R Jacobson, Julio D Duarte, William C Nichols, Joe G N Garcia, Ankit A Desai
BACKGROUND: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1...
May 2, 2024: Circulation